Examination of stimulation mechanism and strength-interval curve in cardiac tissue

Abstract

Understanding the basic mechanisms of excitability through the cardiac cycle is critical to both the development of new implantable cardiac stimulators and improvement of the pacing protocol. Although numerous works have examined excitability in different phases of the cardiac cycle, no systematic experimental research has been conducted to elucidate the correlation among the virtual electrode polarization pattern, stimulation mechanism, and excitability under unipolar cathodal and anodal stimulation. We used a high-resolution imaging system to study the spatial and temporal stimulation patterns in 20 Langendorff-perfused rabbit hearts. The potential-sensitive dye di-4-ANEPPS was utilized to record the electrical activity using epifluorescence. We delivered S1-S2 unipolar point stimuli with durations of 2-20 ms. The anodal S-I curves displayed a more complex shape in comparison with the cathodal curves. The descent from refractoriness for anodal stimulation was extremely steep, and a local minimum was clearly observed. The subsequent ascending limb had either a dome-shaped maximum or was flattened, appearing as a plateau. The cathodal S-I curves were smoother, closer to a hyperbolic shape. The transition of the stimulation mechanism from break to make always coincided with the final descending phase of both anodal and cathodal S-I curves. The transition is attributed to the bidomain properties of cardiac tissue. The effective refractory period was longer when negative stimuli were delivered than for positive stimulation. Our spatial and temporal analyses of the stimulation patterns near refractoriness show always an excitation mechanism mediated by damped wave propagation after S2 termination.

Intracellular Calcium and the Mechanism of the Dip in the Anodal Strength-Interval Curve in Cardiac Tissue

“…17 However, the cathodal and anodal SI curves started 127 ms earlier than the respective SI curves with the Beeler-Reuter model because of the different APDs in the two models. The calculated anodal SI curve has the same shape as measured experimentally by Sidorov et al 12 The curve has a dip, plateau phase, and descent at the end of the relative refractory period. The presence of the dip in the bidomain simulations but not the space-clamped simulations or the simulations with equal-anisotropy-ratios suggests the dominance of the electrotonic interaction between virtual anodes and cathodes over I NCX as a mechanism for the dip.…”

“…Thus, the dip in the anodal SI curve arises from the electrotonic interaction of hyperpolarized tissue under the anode and adjacent depolarized tissue. Sidorov et al 12 performed optical mapping studies of rabbit hearts and verified that the dip occurs during break excitation.…”

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

“…The detailed description of the heart preparation has been published previously (52)(53)(54). The animals were preanesthetized with ketamine (50 mg/kg), heparinized (1,000 units), and anesthetized with pentobarbital sodium (60 mg/kg).…”

Numerical Simulations of Cardiac Tissue Excitation and Pacing Using the Bidomain Model

“…The dip of the anodal strength-interval curve is especially prominent for longer pulse durations. Sidorov et al [86] studied the strength-interval curves using optical mapping, and found similar behavior as predicted by the bidomain model. This mechanism for the dip in the anodal strengthinterval curve implies that the dip should occur over the same interval range as the repolarization phase of the previous action potential, at which time the tissue is recovering from refractoriness.…”